TY - JOUR
T1 - CXCL17 chemokine–dependent mobilization of CXCR8 + CD8 + effector memory and tissue-resident memory T cells in the vaginal mucosa is associated with protection against genital herpes
AU - Srivastava, Ruchi
AU - Hernández-Ruiz, Marcela
AU - Khan, Arif A.
AU - Fouladi, Mona A.
AU - Kim, Grace J.
AU - Ly, Vincent T.
AU - Yamada, Taikun
AU - Lam, Cynthia
AU - Sarain, Sheilouise A.B.
AU - Boldbaatar, Undariya
AU - Zlotnik, Albert
AU - Bahraoui, Elmostafa
AU - BenMohamed, Lbachir
N1 - Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018/4/15
Y1 - 2018/4/15
N2 - Circulating conventional memory CD8 + T cells (i.e., the CD8 + effector memory T [T EM ] cell and CD8 + central memory T [T CM ] cell subsets) and the noncirculating CD8 + tissue-resident memory T (T RM ) cell subset play a critical role in mucosal immunity. Mucosal chemokines, including the recently discovered CXCL17, are also important in mucosal immunity because they are homeostatically expressed in mucosal tissues. However, whether the CXCL17 chemokine contributes to the mobilization of memory CD8 + T cell subsets to access infected mucosal tissues remains to be elucidated. In this study, we report that after intravaginal HSV type 1 infection of B6 mice, we detected high expression levels of CXCL17 and increased numbers of CD44 high CD62L low CD8 + T EM and CD103 high CD8 + T RM cells expressing CXCR8, the cognate receptor of CXCL17, in the vaginal mucosa (VM) of mice with reduced genital herpes infection and disease. In contrast to wild-type B6 mice, the CXCL17 2 / 2 mice developed 1) fewer CXCR8 + CD8 + T EM and T RM cells associated with more virus replication in the VM and more latency established in dorsal root ganglia, and 2) reduced numbers and frequencies of functional CD8 + T cells in the VM. These findings suggest that the CXCL17/CXCR8 chemokine pathway plays a crucial role in mucosal vaginal immunity by promoting the mobilization of functional protective CD8 + T EM and CD8 + T RM cells, within this site of acute and recurrent herpes infection.
AB - Circulating conventional memory CD8 + T cells (i.e., the CD8 + effector memory T [T EM ] cell and CD8 + central memory T [T CM ] cell subsets) and the noncirculating CD8 + tissue-resident memory T (T RM ) cell subset play a critical role in mucosal immunity. Mucosal chemokines, including the recently discovered CXCL17, are also important in mucosal immunity because they are homeostatically expressed in mucosal tissues. However, whether the CXCL17 chemokine contributes to the mobilization of memory CD8 + T cell subsets to access infected mucosal tissues remains to be elucidated. In this study, we report that after intravaginal HSV type 1 infection of B6 mice, we detected high expression levels of CXCL17 and increased numbers of CD44 high CD62L low CD8 + T EM and CD103 high CD8 + T RM cells expressing CXCR8, the cognate receptor of CXCL17, in the vaginal mucosa (VM) of mice with reduced genital herpes infection and disease. In contrast to wild-type B6 mice, the CXCL17 2 / 2 mice developed 1) fewer CXCR8 + CD8 + T EM and T RM cells associated with more virus replication in the VM and more latency established in dorsal root ganglia, and 2) reduced numbers and frequencies of functional CD8 + T cells in the VM. These findings suggest that the CXCL17/CXCR8 chemokine pathway plays a crucial role in mucosal vaginal immunity by promoting the mobilization of functional protective CD8 + T EM and CD8 + T RM cells, within this site of acute and recurrent herpes infection.
UR - http://www.scopus.com/inward/record.url?scp=85046767843&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1701474
DO - 10.4049/jimmunol.1701474
M3 - Artículo
C2 - 29549178
AN - SCOPUS:85046767843
SN - 0022-1767
VL - 200
SP - 2915
EP - 2926
JO - Journal of immunology (Baltimore, Md. : 1950)
JF - Journal of immunology (Baltimore, Md. : 1950)
IS - 8
ER -